Bone quality factors other than bone density determine more than half of the propensity to fracture in patients suffering osteoporosis. A number of candidate bone quality defects have been described, but their relative importance in patients who are suffering fractures has not yet been explored. The purpose of this study is to characterize these defects in bone quality that contribute to low trauma fractures in postmenopausal women. The general hypothesis is: In postmenopausal women with osteopenia, measured values of bone quality factors differentiate those who sustain low-trauma fractures from those who do not. We will use a cross- sectional case-control design to test three primary hypotheses: Postmenopausal women with osteopenia who sustain low-trauma fractures have: 1. Increased bone remodeling; 2. Reduced trabecular connectivity; 3. Defective intrinsic material properties of bone tissue. The secondary hypothesis is: Postmenopausal women with low-trauma fractures have reduced bone quality as indicated by a battery of clinical measures compared to those that have not fractured. We will recruit a total of 120 postmenopausal women between ages 45 and 70 with the lower of hip or spine T scores (DXA) between -1.5 and -2.5 in a case-control study design. Cases will include 60 of these otherwise healthy post-menopausal women who have been fracturing from little or no trauma during the previous 4 years. Controls will include 60 post-menopausal women with similar BMD and age who are not fracturing, do not have a history of low-trauma fracture and are healthy. We will recruit control subjects one-by-one as we recruit the cases, matching the control subjects to within 5 years of the age, and within 10% of both the hip and spine BMD in each case. We will obtain hip structural analyses from dual energy absorptiometry, magnetic resonance images of the radius, quantitative computed tomography of the hip and spine, and two transilial bone biopsy specimens from each subject. The relevance of this study is that in order to develop effective preventive and treatment measures for the ~40 million persons in the U.S. who have osteoporosis and risk of fracture, we must fully understand the cause. This project proposes to study those factors that determine >50% of the risk of fracture, and that are not determined by BMD. We believe that this will be the most comprehensive examination of bone quality defects as a cause of fracture that can possibly be undertaken at this time. PUBLIC HEALTH RELEVANCE: The purpose of this human study is to characterize defects in bone quality, independent of bone mass, that contribute to low trauma fractures in postmenopausal women. Whatever the outcome, this project will feed information to investigators on future directions of basic research into the defects in bone quality that weaken the skeleton in humans. This project will point the direction for research into the cause of fractures and the development of diagnostic methods to predict risk of fractures before they occur, and into development of surrogate measures for fracture that could be used in human treatment trials.